¹³CO2 isotope tracing combined with real-time indirect calorimetry reveals enhanced aerobic glycolysis in cancer and disrupted glucose utilization in diet-induced obesity (DIO). • TSE Systems - Together through Science and EngineeringTSE Systems

In this recent study from the lab of Selma Masri at UC Irvine, the researchers used a unique new approach in collaboration with TSE Systems to quantify the changes in glucose utilization in two prevalent disease models. They assessed real-time glucose utilization in lung cancer-induced cachexia and DIO mouse models using a U-¹³C glucose tracer and stable isotope sensors integrated into the sophisticated PhenoMaster indirect calorimetry system.

Metabolic rewiring is a hallmark feature prevalent in cancer cells and insulin resistance (IR) associated with diet-induced obesity (DIO).

Metabolic rewiring is one of the hallmarks of cancer that promotes tumor proliferation in low-nutrient and oxygen conditions. Metabolic reprogramming includes the Warburg effect or aerobic glycolysis and the recycling of lactate, amino acids, and ammonia to support cancer cell growth and progression. Interestingly, lactate is the primary fuel source of the mitochondrial tricarboxylic acid (TCA) cycle in the human lung and many other tissues (references in the paper). The Warburg effect has been demonstrated in most tumors and, in clinical applications, has been leveraged for imaging, such as fluoro-D-glucose Positron Emission Tomography (18F-FDG-PET) to detect glucose uptake in tumors. Studies from humans and mice show that increased glucose and lactate oxidation in the Mitochondria is characteristic of the altered metabolism of lung tumors and other tumor types.

Glucose homeostasis is also disrupted in metabolic syndrome, obesity, and type 2 diabetes. Consumption of high-fat and high-sugar diets is one of the major causes of DIO and is attributed to IR, which is characterized by elevated blood glucose and triglyceride levels.

For the first time, the data in this study show real-time elevated tracer ¹³CO2 expired by tumor-bearing (TB) mice and a reduction in exhaled ¹³CO2 in the DIO model. These findings illustrate high glucose uptake and consumption in TB animals and decreased glucose uptake and oxidation in obese mice with an Insulin resistance (IR) phenotype.

This work has important translational implications for the utility of stable isotopes in breath-based detection of glucose homeostasis in models of (lung) cancer progression and DIO in Humans.

Schematic diagram of a stable isotope breath test study in mice using U-¹³C glucose.